Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing

Genes and Development - Tập 19 Số 4 - Trang 489-501 - 2005
Chryssa Kanellopoulou1, Stefan A. Muljo2,3, Andrew L. Kung1, Shridar Ganesan1, Ronny Drapkin1, Thomas Jenuwein4, David M. Livingston1, Klaus Rajewsky2,3
1The Dana-Farber Cancer Institute, Department of Cancer Biology and
2Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115 USA
3The CBR Institute for Biomedical Research and
4Research Institute of Molecular Pathology, The Vienna Biocenter, A-1030 Vienna, Austria

Tóm tắt

Dicer is the enzyme that cleaves double-stranded RNA (dsRNA) into 21–25-nt-long species responsible for sequence-specific RNA-induced gene silencing at the transcriptional, post-transcriptional, or translational level. We disrupted the dicer-1 (dcr-1) gene in mouse embryonic stem (ES) cells by conditional gene targeting and generated Dicer-null ES cells. These cells were viable, despite being completely defective in RNA interference (RNAi) and the generation of microRNAs (miRNAs). However, the mutant ES cells displayed severe defects in differentiation both in vitro and in vivo. Epigenetic silencing of centromeric repeat sequences and the expression of homologous small dsRNAs were markedly reduced. Re-expression of Dicer in the knockout cells rescued these phenotypes. Our data suggest that Dicer participates in multiple, fundamental biological processes in a mammalian organism, ranging from stem cell differentiation to the maintenance of centromeric heterochromatin structure and centromeric silencing.

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Genes and Development

Tập 19 Số 4

489-501

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